Promising potential of boron compounds against Glioblastoma: In Vitro antioxidant, anti-inflammatory and anticancer studies

Türkez, Hasan; Arslan, Mustafa; Tatar, Abdülgani; Mardinoğlu, Adil

doi:10.1016/j.neuint.2021.105137

Cited by 43 publications

(37 citation statements)

References 55 publications

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“…What's more, ROS levels increased at IC 50 dose of BA. It was found that BA increased TAS levels without changing TOS levels in U‐87MG cells 12 . In the previous reports, Boric acid and boron derivatives did not increase MDA levels in healthy cells 19 .…”

Section: Discussionmentioning

confidence: 74%

“…Boron, boric acid (BA) and other boron‐derived compounds that we intakes bodies as trace elements have antioxidant, anti‐inflammatory and anti‐apoptotic properties in environmental studies 11,12 . According to our previous in vivo findings, 50–100 mM BA doses have a protective and therapeutic impact however it shows antiproliferative activity at high concentrations in cancer cells in vitro ( 13 ; Kar et al 8,9 ).…”

Section: Introductionmentioning

confidence: 96%

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The dual role of boron in vitro neurotoxication of glioblastoma cells via SEMA3F/NRP2 and ferroptosis signaling pathways

Kar¹,

Hacıoğlu

Kaçar

2022

Environmental Toxicology

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Glioblastoma multiform (GBM) is a malignant tumor cancer that originates from the star‐shaped glial support tissues, namely astrocytes, and it is associated with a poor prognosis in the brain. The GBM has no cure, and chemotherapy, radiation therapy, and immunotherapy are all ineffective. A certain dose of Boric acid (BA) has many biochemical effects, conspicuously over antioxidant/oxidant rates. This article sought to investigate the modifies of various doses of BA on the glioblastoma concerning cytotoxicity, ferroptosis, apoptosis, and semaphorin–neuropilin signaling pathway. The Cytotoxic activity and cell viability of BA (0.39–25 mM) in C6 cells were tested at 24, 48, and 72 h using 3‐(4,5‐dimethylthiazol, 2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT). The IC50 concentration of BA at 1.56 mM was found and cell lysate used for biochemical analysis. Glutathione peroxidase 4 (GPx4) and ACLS4 levels of ferroptosis, levels of total antioxidant (TAS) and oxidant (TAS) parameters, malondialdehyde (MDA), apoptotic proteins as caspase 3 (CASP3) and caspase 7 (CASP7) were measured. The ferroptosis, semaphoring–neuropilin, apoptotic pathway markers and cell counts were analyzed with flow cytometry, Q‐PCR, Western and Elisa technique in the C6 cell lysate. BA triggered ferroptosis in the C6 cells dose‐dependently, affecting the semaphorin pathway, so reducing proliferation with apoptotic compared with untreated cell as control group (p < .05). This study revealed that BA, defined as trace element and natural compound, incubated ferroptosis, total oxidant molecules, and caspase protein in a dose‐dependently by disrupting SEMA3F in tumor cells.

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Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 96%

The dual role of boron in vitro neurotoxication of glioblastoma cells via SEMA3F/NRP2 and ferroptosis signaling pathways

Kar¹,

Hacıoğlu

Kaçar

2022

Environmental Toxicology

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“…Boron compounds were investigated in different studies, and it has been shown that various types of boron-based molecules could be promising biomaterials in medical applications with a low cytotoxic profile [ 8 , 9 , 10 , 11 , 12 ]. Moreover, increasing attention to the biological use of hexagonal boron nitride (hBN) nanomaterials for medical applications in different areas such as biosensors, tissue engineering and especially drug delivery put forth favorable features of boron molecules in treatment of neurodegenerative diseases [ 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Boron Nitride Nanoparticles Loaded with a Boron-Based Hybrid as a Promising Drug Carrier System for Alzheimer’s Disease Treatment

Çağlar

Arslan

Öner

et al. 2022

IJMS

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The search for an innovative and effective drug delivery system that can carry and release targeted drugs with enhanced activity to treat Alzheimer’s disease has received much attention in the last decade. In this study, we first designed a boron-based drug delivery system for effective treatment of AD by integrating the folic acid (FA) functional group into hexagonal boron nitride (hBN) nanoparticles (NPs) through an esterification reaction. The hBN-FA drug carrier system was assembled with a new drug candidate and a novel boron-based hybrid containing an antioxidant as BLA, to constitute a self-assembled AD nano transport system. We performed molecular characterization analyses by using UV-vis spectroscopy, Fourier transform infrared spectrophotometer (FTIR), scanning electron microscope (SEM), Energy-dispersive X-ray spectroscopy (EDS) and Zeta potential investigations. Second, we tested the anti-Alzheimer properties of the carrier system on a differentiated neuroblastoma (SHSY5-Y) cell line, which was exposed to beta-amyloid (1–42) peptides to stimulate an experimental in vitro AD model. Next, we performed cytotoxicity analyses of synthesized molecules on the human dermal fibroblast cell line (HDFa) and the experimental AD model. Cytotoxicity analyses showed that even higher concentrations of the carrier system did not enhance the toxicological outcome in HDFa cells. Drug loading analyses reported that uncoated hBN nano conjugate could not load the BLA, whereas the memantine loading capacity of hBN was 84.3%. On the other hand, memantine and the BLA loading capacity of the hBN-FA construct was found to be 95% and 97.5%, respectively. Finally, we investigated the neuroprotective properties of the nano carrier systems in the experimental AD model. According to the results, 25 µg/mL concentrations of hBN-FA+memantine (94% cell viability) and hBN-FA+BLA (99% cell viability) showed ameliorative properties against beta-amyloid (1–42) peptide toxicity (50% cell viability). These results were generated through the use of flow cytometry, acetylcholinesterase (AChE) and antioxidant assays. In conclusion, the developed drug carrier system for AD treatment showed promising potential for further investigations and enlightened neuroprotective capabilities of boron molecules to treat AD and other neurodegenerative diseases. On the other hand, enzyme activity, systematic toxicity analyses, and animal studies should be performed to understand neuroprotective properties of the designed carrier system comprehensively.

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“…Recent studies indicated positive health impacts due to B intake on humans and animals. These key biological effects include antioxidant [ 18 ], anti-mutagenic [ 19 ], anti-microbial [ 20 ], anti-inflammatory [ 21 ], anticancer [ 22 ], neuroprotective [ 23 ] action potential and metal chelating features [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Ameliorative Effects by Hexagonal Boron Nitride Nanoparticles against Beta Amyloid Induced Neurotoxicity

et al. 2022

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Alzheimer’s disease (AD) is considered as the most common neurodegenerative disease. Extracellular amyloid beta (Aβ) deposition is a hallmark of AD. The options based on degradation and clearance of Aβ are preferred as promising therapeutic strategies for AD. Interestingly, recent findings indicate that boron nanoparticles not only act as a carrier but also play key roles in mediating biological effects. In the present study, the aim was to investigate the effects of different concentrations (0–500 mg/L) of hexagonal boron nitride nanoparticles (hBN-NPs) against neurotoxicity by beta amyloid (Aβ1-42) in differentiated human SH-SY5Y neuroblastoma cell cultures for the first time. The synthesized hBN-NPs were characterized by X-ray diffraction (XRD) measurements, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Aβ1-42-induced neurotoxicity and therapeutic potential by hBN-NPs were assessed on differentiated SH-SY5Y cells using MTT and LDH release assays. Levels of total antioxidant capacity (TAC) and total oxidant status (TOS), expression levels of genes associated with AD and cellular morphologies were examined. The exposure to Aβ1-42 significantly decreased the rates of viable cells which was accompanied by elevated TOS level. Aβ1-42 induced both apoptotic and necrotic cell death. Aβ exposure led to significant increases in expression levels of APOE, BACE 1, EGFR, NCTSN and TNF-α genes and significant decreases in expression levels of ADAM 10, APH1A, BDNF, PSEN1 and PSENEN genes (p < 0.05). All the Aβ1-42-induced neurotoxic insults were inhibited by the applications with hBN-NPs. hBN-NPs also suppressed the remarkable elevation in the signal for Aβ following exposure to Aβ1-42 for 48 h. Our results indicated that hBN-NPs could significantly prevent the neurotoxic damages by Aβ. Thus, hBN-NPs could be a novel and promising anti-AD agent for effective drug development, bio-nano imaging or drug delivery strategies.

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Promising potential of boron compounds against Glioblastoma: In Vitro antioxidant, anti-inflammatory and anticancer studies

Cited by 43 publications

References 55 publications

The dual role of boron in vitro neurotoxication of glioblastoma cells via SEMA3F/NRP2 and ferroptosis signaling pathways

The dual role of boron in vitro neurotoxication of glioblastoma cells via SEMA3F/NRP2 and ferroptosis signaling pathways

Boron Nitride Nanoparticles Loaded with a Boron-Based Hybrid as a Promising Drug Carrier System for Alzheimer’s Disease Treatment

Ameliorative Effects by Hexagonal Boron Nitride Nanoparticles against Beta Amyloid Induced Neurotoxicity

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